The overall objective of my research project is to study, with ultrastructural techniques, the pathways by which macromolecules cross the wall of small blood vessels and lymphatics. The techniques require the use of tracers of various sizes which can be visualized with the electron microscope. My project has three objectives. The first objective is to examine the pathway of lymphatic drainage of the peritoneal cavity. Peritoneal fluid leaves the cavity chiefly via initial uptake by terminal lymphatic lacunae located on the undersurface of the diaphragm and subsequent transfer via parasternal lymphatic vessels to the right lymphatic duct. I propose to examine how tracers cross the three barriers between the peritoneal cavity and the lumen of the lymphatic lacunae, i.e., the mesothelium covering the lacunae, the submesothelial connective tissue, and the endothelium lining the lacunae. The second objective is to localize, within the microcirculation of skeletal muscle, the microvessel which is most permeable to intravenously injected tracers and then determine the ultrastructural characteristics that accounts for its greater permeability. The third is to analyze factors that could influence the vesicular transfer of tracers across the wall of muscle capillaries. I shall use a rat heart perfused with tracer solutions in vitro to assess how factors which alter metabolism, how variations in the ionic environment such as low Ca ion concentration, and how vasoactive agents such as histamine affect vesicular transfer of the tracers and passage of tracers through endothelial junctions.